NEW ORLEANSA less frequent dosing schedule of recombinant human
erythropoietin (epoetin alfa, Epogen, Procrit) may offer effective
and more convenient treatment for the fatigue and malaise associated
with cancer therapies, said George D. Demetri, MD, medical director,
Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute.
Speaking at a satellite symposium preceding the 41st Annual Meeting
of the American Society of Hematology (ASH), Dr. Demetri pointed out
that the commonplace three-times-weekly erythropoietin dosing
strategy is derived from the typical schedule for dialysis patients,
not from research into optimal dosing. Equivalent efficacy can be
achieved, he said, with once-weekly dosing, provided that higher
doses are used.
Considering what has been learned about the use of epoetin alfa in
the renal dialysis setting, not enough is being done for cancer
patients, Dr. Demetri suggested. Beyond avoiding transfusions,
end-stage renal disease patients have demonstrated improvements in
quality of life, exercise tolerance, and physical and cognitive
function with epoetin alfa.
While use of epoetin alfa has become a reasonable thing to
think about for cancer patients, treatment for anemia has been
too often ignored in the past or delayed until transfusion of red
cells was required, he said.
Randomized controlled trials of epoetin alfa conducted 10 years ago
among cancer patients receiving or not receiving chemotherapy showed
anemia responding in all groups. Other studies have shown that mean
weekly hematocrits in chemotherapy patients diverge sharply with use
of epoetin alfa, compared with placebo, as soon as 2 weeks after the
inception of therapy.
Dr. Demetris own study (J Clin Oncol 16:3412-3425, 1998)
among more than 2,000 patients demonstrated a direct correlation
between increasing hemoglobin levels and improved energy, activity,
and overall quality of life. Analysis of an even larger database
covering more than 4,500 cancer patients further confirms these
benefits, Dr. Demetri said.
Patients are telling us, with remarkable consistency, that as
hemoglobin levels improve, they somehow feel better and are
functioning better, he commented. He noted, however, that
oncology patients require higher doses than renal failure patients,
and that more than half do not respond. We need to find out
which patients have the most benefit, Dr. Demetri added.
NESP (novel erythropoiesis stimulating protein) is an investigational
molecule rationally designed as a hyperglycol-sylated substance with
delayed clearance. Phase III studies of the new agent are promising,
Dr. Demetri said. Trials in 522 dialysis patients have shown that
once-weekly or even biweekly NESP dosing increases hemoglobin levels
similarly to epoetin alfa dosed once weekly to three times weekly.
The half-life of NESP given intravenously or subcutaneously is
two- to threefold longer than conventional epoetin alfa, he said.
No antibodies against NESP or endogenous human erythropoietin have
been detected in patients receiving NESP, he said. Ongoing research
aims to identify the least intrusive dosing schedule that will yield
clinically significant efficacy.
Dr. Demetri pointed out other important research questions concerning
fatigue management: Can we stimulate erythropoiesis in patients
refractory to epoetin alfa or NESP? Beyond stimulation of
erythropoiesis, can other mediators of fatigue and malaise be
reversed, leading to more comprehensive fatigue management in cancer
He urged further study aimed at determining whether improved
functional status in fatigued cancer patients leads to economic
benefits from either return to employment or reductions in health
Dr. Demetri commented, Patients are very willing to pay for
alternative medicines that dont have the biology and research
behind them that erythropoiesis has. But nothing is more natural than
stimulating erythropoiesis with your own normal hormonal